Introduction: Spiropyranopyrazole derivatives are spiro-heterocycles of pharmacologi-cal interest due to their wide-ranging bioactivities, including antimicrobial, anticancer, and anti-inflammatory properties. However, conventional synthesis approaches are often time-consuming, environmentally taxing, and involve hazardous reagents. This study aims to develop an eco-friendly, efficient synthetic route using ultrasound-assisted conditions in water with DMAP as an organocatalyst. Method: A green one-pot multicomponent reaction was employed to synthesize spiropyranopyra-zole derivatives using ethyl acetoacetate, hydrazine hydrate, isatin derivatives, and malononitrile under ultrasonic irradiation. DMAP (20 mol%), in aqueous medium, was used as a catalyst. The synthesized compounds (5a–5j) were characterized via FTIR, ¹H NMR, ¹³C NMR, and elemental analysis. Theoretical validation was performed using DFT calculations at the B3LYP/6-311+G(d,p) level. ADME predictions were conducted to assess pharmacokinetic behavior and drug-likeness. objective: The study aims to develop a green, ultrasound-assisted, one-pot synthesis of spiropyranopyrazole derivatives using 4-(Dimethylamino)pyridine (DMAP) as an organocatalyst in water. The research further investigates the structural, electronic, and pharmacokinetic properties of the synthesized compounds through spectroscopic characterization, density functional theory (DFT) calculations, and ADME (Absorption, Distribution, Metabolism, and Excretion) analysis. Results: The ultrasound-assisted protocol delivered excellent yields (90–96%) within 1 hour with-out the use of toxic solvents or chromatographic purification. Reaction optimization confirmed DMAP in water as the most effective condition. Theoretical DFT calculations supported the stabil-ity and electronic properties of the synthesized compounds. ADME studies indicated high oral bi-oavailability, good solubility, favorable lipophilicity, and compliance with major drug-likeness fil-ters for most derivatives. Discussion: The green synthetic strategy demonstrated excellent efficiency across various substi-tuted isatins, highlighting its robustness. DFT results correlated well with spectroscopic data, con-firming structural integrity and predicting potential biological interactions. ADME profiling further reinforced the therapeutic potential of the compounds. Conclusion: This study offers a sustainable, high-yielding, and rapid methodology for synthesizing spiropyranopyrazole derivatives using water as a green solvent. Combined spectroscopic, compu-tational, and pharmacokinetic evaluations establish the synthesized compounds as promising can-didates for future pharmaceutical development.
Giri et al. (Mon,) studied this question.